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Organosilicon compounds are important reagents and synthetic intermediates that play a key role in the construction of new materials and complex products. Here we show a highly diastereoselective rhodium‐catalyzed cycloisomerization of 1,6‐dienes, in which the use of (EtO)3SiH accelerates the intramolecular cyclization reaction to afford a novel spiro‐fused succinimide and pyrazolone derivatives in moderate to excellent yields as a single diastereoisomer. The proposed mechanism involves an active Rh−H species from the hydrosilane that is the H‐donor in this spiro‐type cycloisomerization reaction. [ABSTRACT FROM AUTHOR]

Aims Inflammation and apoptosis play important roles in increasing vascular permeability following subarachnoid hemorrhage (SAH). The objective of this study was to evaluate whether urinary trypsin inhibitor (UTI), a serine protease inhibitor, attenuates vascular permeability by its antiinflammatory and antiapoptotic effects after experimental SAH. Methods Subarachnoid hemorrhage models were established in adult male Sprague-Dawley rats by endovascular perforation. UTI was administered by intraperitoneal injection immediately following SAH. Brain edema was assessed by magnetic resonance imaging (MRI) at 24 h after SAH. Neurological deficits, brain water content, vascular permeability, malondialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity were evaluated. Immunohistochemical staining and Western blot were used to explore the underlying protective mechanism of UTI. Results Urinary trypsin inhibitor 50,000 U/kg significantly attenuated brain edema and neurological deficits and reduced vascular permeability at 24 h after SAH. MDA concentration and MPO activity in hippocampus were significantly decreased with UTI treatment. Furthermore, the levels of phosphorylated JNK, NF-κB (p65), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and proapoptotic protein p53, caspase-3 were elevated in the microvascular endothelial cells of the hippocampus after SAH, which were alleviated with UTI treatment. Conclusion Urinary trypsin inhibitor reduced vascular permeability after SAH through its antiinflammatory and antiapptotic effects via blocking the activity of JNK, NF-κB, and p53. [ABSTRACT FROM AUTHOR]

Aims Programmed Cell Death 5 ( PDCD5) is a protein that accelerates apoptosis in different types of cells in response to various stimuli and is down-regulated in many cancer tissues. We hypothesized in this study that down-regulating PDCD5 can protect the brain from ischemic damage by inhibiting PDCD5-induced apoptotic pathway. Methods One hundred and sixty male Sprague-Dawley rats were randomly assigned to five groups: Sham surgery (n = 25), MCAO (n = 45), MCAO+rh PDCD5 (Rh PDCD5) (n = 30), MCAO+control si RNA (n = 30), and MCAO+ PDCD5 si RNA (n = 30). At 24 h following MCAO, immunohistochemistry and Western blot were performed. Results PDCD5 si RNA reduced the infarct volume, improved neurological deficits, improved cerebral blood flow ( CBF), and reduced Evans blue extravasation. Meanwhile, over-expression of PDCD5 protein with recombinant human PDCD5 (rh PDCD5) had an opposite effect. Immunohistochemistry and Western blot demonstrated PDCD5 si RNA decreased the expressions of key proapoptotic proteins such as p53, Bax/Bcl-2, and cleaved caspase-3 in the penumbra areas, whereas rh PDCD5 increased cell apoptosis. Double fluorescence labeling showed the positive immunoreactive materials of PDCD5 were partly colocalized with MAP2, GFAP, CD34, p53, and caspase-3 in the penumbra areas in brain. Conclusions PDCD5-induced apoptosis and over-expression of PDCD5 are harmful to the ischemic neurons in vivo. Meanwhile, the inhibition of PDCD5 may be protective via reducing the apoptotic-related protein such as p53, Bax, and caspase-3. This observation may have potential for the treatment of ischemic cerebral stroke. [ABSTRACT FROM AUTHOR]

SUMMARY Aims: To investigate the mechanism behind cytotoxic edema formation following subarachnoid hemorrhage (SAH). Methods: We explored the role of aquaporin-4 (AQP4), inwardly rectifying K+ 4.1 (Kir4.1) channels and their upstream orchestrators p53 and p38MAPK in this process. A p53 inhibitor, pifithrin-α (PFT-α) was administered intraperitoneally to rats undergoing SAH by endovascular perforation. Totally, 98 male SD rats were categorized into sham, SAH, SAH+ dimethyl sulfoxide (DMSO), SAH+ 0.2 or 2.0 mg/kg PFT-α groups. At 24 h after SAH, MRI (diffusion-weighted imaging [DWI]), immunohistochemistry, and Western blot were used. Results: MRI (DWI) showed a significant cytotoxic edema in the brain following SAH with PFT-α therapy reducing it. Immunohistochemistry and Western blot showed an increased level of p53, phosphorylated-p38MAPK and AQP4 and a reduced level of Kir4.1; all of which could be reversed following PFT-α treatment. Treble labeling staining revealed colocalization of p53 with phosphorylated-p38MAPK and unmatched expression of AQP4 and Kir4.1 within astrocyte cells. Conclusion: These results indicated p53 mediates the formation of cytotoxic edema in the brain following SAH; an uncoupling expression of AQP4 and Kir4.1 on astrocytic end feets orchestrated by p38MAPK was partly responsible. [ABSTRACT FROM AUTHOR]

Aims: To investigate the mechanism behind cytotoxic edema formation following subarachnoid hemorrhage (SAH)., Methods: We explored the role of aquaporin-4 (AQP4), inwardly rectifying K(+) 4.1 (Kir4.1) channels and their upstream orchestrators p53 and p38MAPK in this process. A p53 inhibitor, pifithrin-α (PFT-α) was administered intraperitoneally to rats undergoing SAH by endovascular perforation. Totally, 98 male SD rats were categorized into sham, SAH, SAH+ dimethyl sulfoxide (DMSO), SAH+ 0.2 or 2.0 mg/kg PFT-α groups. At 24 h after SAH, MRI (diffusion-weighted imaging [DWI]), immunohistochemistry, and Western blot were used., Results: MRI (DWI) showed a significant cytotoxic edema in the brain following SAH with PFT-α therapy reducing it. Immunohistochemistry and Western blot showed an increased level of p53, phosphorylated-p38MAPK and AQP4 and a reduced level of Kir4.1; all of which could be reversed following PFT-α treatment. Treble labeling staining revealed colocalization of p53 with phosphorylated-p38MAPK and unmatched expression of AQP4 and Kir4.1 within astrocyte cells., Conclusion: These results indicated p53 mediates the formation of cytotoxic edema in the brain following SAH; an uncoupling expression of AQP4 and Kir4.1 on astrocytic end feet orchestrated by p38MAPK was partly responsible., (© 2012 Blackwell Publishing Ltd.)